The activity of
dalbavancin, a representative of the
lipoglycopeptide antibiotics, alone and in combination with
rifampicin, was investigated against
meticillin-resistant Staphylococcus aureus (MRSA) in a
foreign-body infection model in guinea pigs. The MIC, MBC and time-kill profile of
dalbavancin were determined for MRSA ATCC 43300 in the logarithmic (MBC(log)) and stationary (MBC(stat)) growth phases. The pharmacokinetic profile of
dalbavancin was determined in sterile cage fluid in guinea pigs. The activity of intraperitoneal
dalbavancin (40, 60 or 80 mg/kg as a single dose),
rifampicin (12.5 mg/kg/12 h for 4 days) and their combination was assessed against planktonic and biofilm MRSA. The MIC of
dalbavancin was 0.078 mg/L; MBC(log) and MBC(stat) were both >128× MIC. In time-kill studies, bacterial reduction of 3log(10)CFU/mL was achieved after 48 h at ≥32× MIC (logarithmic growth) and at ≥1× MIC (stationary growth).
Dalbavancin was neither synergistic nor antagonistic with
rifampicin, and prevented the emergence of
rifampicin resistance in vitro. The half-life of
dalbavancin in cage fluid was 35.8-45.4 h and the concentration remained above the MIC of MRSA during 7 days after a single dose.
Dalbavancin reduced planktonic MRSA in cage fluid at high dose (60 mg/kg and 80 mg/kg) but failed to eradicate biofilm MRSA from cages. In combination with
rifampicin,
dalbavancin at 80 mg/kg cured 36% of infected cages, and emergence of
rifampicin resistance was completely prevented.
Dalbavancin at 80 mg/kg and in combination with
rifampicin eradicated approximately one-third of cage-associated MRSA
infections and prevented emergence of
rifampicin resistance.